Soybean consumption is associated with a reduced incidence of breast cancer in epidemiological studies, although the mechanism of this effect is unknown. In previous mechanistic studies in women we found that consumption for one month of soymilk containing significant quantities of the isoflavones, daidzein and genistein, effectively reduced levels of endogenous ovarian steroids and adrenal androgen, which are recognized risk factors for breast cancer. The reduced levels of steroid hormones induced by soya feeding may decrease breast cell proliferation and thereby explain the breast cancer-protective effects of soya diets. However, because long term ingestion of high-isoflavone forages reduced fertility of sheep, there is concern about the effects of long term soya ingestion on endocrine function in healthy women. Our long term objective is to determine an effective and safe frequency of consumption in healthy women that will produce a positive health benefit: risk ratio. The present studies determine endocrine effects induced by 4-5 months of soya consumption. The first study determines if consumption of soya diets containing 0 or >200mg of isoflavones by 40 regularly cycling women for 5 months will prolong menstrual cycle length and further reduce levels of ovarian hormones and gonadotropins when compared to consumption of non- soya diets. The second study involves 16 postmenopausal women who will consume soymilk for 4 months. Levels of ovarian hormones and gonadotropins in blood, metabolites of phytoestrogens in urine, vaginal cytology, and endometrial histology and thickness by vaginal proble ultrasound, and interrelationship of these determinations before, during and after soya feeding will be determined. These and other ongoing studies will provide information needed to optimize the frequency of phytoestrogen consumption in healthy women and contribute to the design of future prospective trials to determine if a soya diet can favorably influence breast cancer risk in American women.